#*The submission includes studies showing that the product's labeling can be read, understood, and followed by the consumer without the guidance of a health care provider
#*Some drugs are approved initially as OTC drugs, but most are first approved for prescription use and later switched to OTC
==Rx and OTC Regulation==
The FDA process for drug approval is given below
[[Image:FDA Drug Regulation Process.jpg |center|thumb|1100px| [http://www.fda.gov/Drugs/default.htm FDA Drug Regulation Process]]]
* NDA - New Drug Application
* ANDA - Abbreviated New Drug Application
* Full NDA- For a new dosage or formulation such as lower strength than Rx version (for a medication currently available by prescription)
* Supplemental NDA – For a product for which the manufacturer already holds an approved NDA or holds an abbreviated NDA for a closely related product
* Abbreviated NDA – For products that are identical to an existing prescription product
* The switch to OTC is done in a partial or total way. Most switches are partial, a version of the active ingredient remains available on prescription while a specific indication, strength, or dosage form becomes available through the(new NDA) switch application. On the other hand some switches are full, no prescription version of the active ingredient remains which becomes available through (NDA supplement) switch application.
Source:[http://www.fda.gov FDA] , [http://books.google.co.in/books?id=XU1sMK1djVAC&pg=PA22&lpg=PA22&dq=rx-to-otc+switch+full+partial&source=bl&ots=o32Y2RGGOL&sig=6bYHqWf8Qi79E1Tq7-bm340hJ7A&hl=en&sa=X&ei=e3LCUvCiC8WwiQeeg4HgDA&redir_esc=y#v=onepage&q=rx-to-otc%20switch%20full%20partial&f=false Nonprescription Product Therapeutics, Section 1, Chapter 2]
===Prescription Drugs - Branded===
Once a drug has been discovered, the drug manufacturer must test the drug in laboratory and on animals. If it proves effective, the drug is tested in humans to see if it safe and effective.
Once it is demonstrated to be safe, the manufacturer sends a '''New Drug Application (NDA)''' to the FDA to apply for approval. Next come tests in humans to see if the drug is safe and effective when used to treat or diagnose a disease.
'''New Drug Application (NDA)'''
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The NDA application is the vehicle through which drug sponsors formally propose that the FDA approve a new pharmaceutical for sale and marketing in the U.S. The data gathered during the animal studies and human clinical trials of an Investigational New Drug (IND) become part of the NDA.
The goals of the NDA are to provide enough information to permit FDA reviewer to reach the following key decisions:
#Whether the drug is safe and effective in its proposed use(s), and whether the benefits of the drug outweigh the risks.
#Whether the drug's proposed labeling (package insert) is appropriate, and what it should contain.
#Whether the methods used in manufacturing the drug and the controls used to maintain the drug's quality are adequate to preserve the drug's identity, strength, quality, and purity.
The documentation required in an NDA is supposed to tell the drug's whole story, including what happened during the clinical tests, what the ingredients of the drug are, the results of the animal studies, how the drug behaves in the body, and how it is manufactured, processed and packaged.
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NDAs include:
#The drug's test results
#Manufacturing information to demonstrate the company can properly manufacture the drug.
#The company's proposed label for the drug, which should include information about the drug, its uses, and possible risks.
The FDA approves drugs if their benefits outweigh any risks in taking them. Once a drug is approved, its manufacturer can market and then sell it in the U.S.
In approving the drug, the FDA also takes into account the proposed name for it. To protect the safety of the public, it is important that the name not be similar to that of another drug product to prevent against mix-ups. FDA's Division of Medication Error Prevention and Analysis reviews the names.
Source:[http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/NewDrugApplicationNDA/default.htm FDA],[http://pharmacy.about.com/od/TheDrugIndustry/a/The-Fda-Drug-Approval-Process.htm Pharmacy.About]
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===Prescription Drugs – Generic===
Generic drugs are also known as copycat drugs. They are exact replicas of the branded drugs and typically go by their chemical name-Lipitor's generic is called atorvastatin, for example. They do not have a patent.
The manufacturers of generic drugs provide an '''abbreviated new drug application (ANDA)''' to the FDA to receive approval. Since there is already a drug on the market to help consumers, the approval time for generic drugs is typically longer.
The Office of Generic Drugs (OGD), which is a department within the FDA, approves generic drugs.
An Abbreviated New Drug Application (ANDA) is submitted to the FDA when seeking review and approval for a generic drug product. The application is submitted to the FDA's Center for Drug Evaluation and Research, Office of Generic Drugs. If approved, the generic drug may be manufactured and sold in the U.S. market.
Generic drug applications are not typically required to include preclinical (animal) and clinical (human) data to establish safety and effectiveness. An applicant submitting an ANDA must scientifically demonstrate that its product is bioequivalent to the previously approved innovator or brand name drug.
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Source:[http://pharmacy.about.com/od/TheDrugIndustry/a/The-Fda-Drug-Approval-Process.htm Pharmacy.about1], [http://pharma.about.com/od/A/g/Abbreviated-New-Drug-Application.htm Pharmacy.about2]
FDA requires generic drugs to have the same quality and performance as brand name drugs.
#When a generic drug product is approved, it has met rigorous standards established by the FDA with respect to identity, strength, quality, purity, and potency. However, some variability can and does occur during manufacturing, for both brand name and generic drugs. When a drug, generic or brand name, is mass-produced, very small variations in purity, size, strength, and other parameters are permitted. FDA limits how much variability is acceptable.
#Generic drugs are required to have the same active ingredient, strength, dosage form, and route of administration as the brand name product. Generic drugs do not need to contain the same inactive ingredients as the brand name product.
#The generic drug manufacturer must prove its drug is the same as (bioequivalent) the brand name drug. For example, after the patient takes the generic drug, the amount of drug in the bloodstream is measured. If the levels of the drug in the bloodstream are the same as the levels found when the brand name product is used, the generic drug will work the same.
#Through review of bioequivalence data, FDA ensures that the generic product performs the same as its respective brand name product. This standard applies to all generic drugs, whether immediate or controlled release.
#All generic manufacturing, packaging, and testing sites must pass the same quality standards as those of brand name drugs, and the generic products must meet the same exacting specifications as any brand name product. In fact, many generic drugs are made in the same manufacturing plants as brand name drug products.
Source: [http://www.fda.gov/drugs/resourcesforyou/consumers/buyingusingmedicinesafely/understandinggenericdrugs/ucm167991.htm FDA]
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===OTC - Branded & Prescription Drugs===
The FDA's '''Office of Drug Evaluation IV''', Over-the-Counter Drug Products reviews OTC drugs. A Nonprescription Drug Advisory Committee, comprised of up to 14 independent experts selected by the FDA commissioner, assists the FDA in reviewing issues surrounding OTC drugs, including switching drugs from prescription to non-prescription status.
Instead of reviewing the labels and ingredients of all 300,000 OTC drugs now being marketed, the FDA focuses on about 80 different therapeutic classes of drugs, such as analgesics, antacids, antimicrobial, antiperspirants, dental and cough/cold medicines.
The FDA publishes an '''OTC drug monograph''' for each category of drug in the Federal Register. Drug monographs serve as a cook book, or list of recipes, that include acceptable ingredients, formulations, dosages and labeling for each category of drug.The monograph explains the types of ingredients that may be used to treat certain diseases or conditions without a prescription, the appropriate dose and instructions for use, and labeling.
Once a monograph is adopted, companies may develop and market an OTC product without pre-approval from the FDA. Products that do not adhere to the monograph must be reviewed through FDA’s '''New Drug Application''' process.A drug company can also petition the FDA to deviate from the ingredient or labeling requirements of an OTC monograph.
#Over-the-counter (OTC) drugs are drugs that the FDA has decided are safe and appropriate for use without the supervision of a health care professional and can be purchased without a prescription.
#Products conforming to a monograph may be marketed without further FDA clearance, while those that do not must undergo separate review and approval through the "New Drug Approval System".
#OTC products that meet a monograph's requirements may be marketed without FDA review. OTC products that do not fit under an existing monograph must be approved under an application like the '''applications for prescription products'''.
Source:[http://pharma.about.com/od/Over-the-Counter-Medicine/a/Over-The-Counter-Drugs-Theres-A-Recipe-For-That.htm Pharmacy.About1],[http://pharmacy.about.com/od/TheDrugIndustry/a/The-Fda-Drug-Approval-Process.htm Pharmacy.About2]
===Rx to OTC Switch – Regulatory Process===
There are 2 regulatory pathways for getting approval for OTC drugs (Rx to OTC switch and Direct to OTC)
# OTC New Drug Application (NDA)
# OTC Drug Monograph
'''Rx-to-OTC switches'''
The applications differ based on whether the manufacturer wants to switch to OTC completely or partially.
#Full switch (NDA supplement)
#Partial switch (new NDA)
Source:[http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/UCM148055.pdf FDA]
'''Direct-to-OTC'''
#OTC Monographs
#OTC NDA
Source:[http://www.slideshare.net/nkp8490/an-overveiw-on-regulation-of-otc-drug-product-in-different-country OTC Regulation in Different Countries]
'''FDA Applications'''
#An efficacy supplement should be submitted to an approved NDA for a prescription product if the sponsor plans to switch the drug product covered under the NDA to OTC marketing status in its entirety without a change in the previously approved dosage form or route of administration.
#An NDA 505(b)(1) should be submitted if the sponsor is proposing to convert some but not all of the approved prescription indications to OTC marketing status.
#An original NDA (505)(b)(1) or 505(b)(2) needs to be submitted if the sponsor plans to market either a new product OTC whose active substance, indication, or dosage form has never previously been marketed OTC.
'''OTC drug review'''
The OTC drug review was established to evaluate the safety and effectiveness of OTC drug products marketed in the United States before May 11, 1972. It is a three-phase public rulemaking process (each phase requiring a Federal Register publication) resulting in the establishment of standards (monographs or non-monographs) for an OTC therapeutic drug category.
::'''First phase'''
:::The first phase was accomplished by advisory review panels. The panels were charged with reviewing the ingredients in nonprescription drug products to determine whether these ingredients could be generally recognized as safe and effective for use in self-treatment. They were also charged with reviewing claims and recommending appropriate labeling, including therapeutic indications, dosage instructions, and warnings about side effects and preventing misuse.
:::According to the terms of the review, the panels classified ingredients in three categories as follows:
:::#Category I: generally recognized as safe and effective for the claimed therapeutic indication;
:::#Category II: not generally recognized as safe and effective or unacceptable indications;
:::#Category III: insufficient data available to permit final classification
::'''Second phase'''
:::The second phase of the OTC drug review was the agency’s review of ingredients in each class of drugs, based on the panel’s findings, on public comment, and on new data that may have become available. The agency, in turn, publishes its conclusions in the Federal Register in the form of a tentative final monograph. After publication of the tentative final monograph, a period of time is allotted for objections to the agency’s proposal or for requests to be submitted for a hearing before the Commissioner of FDA.
::'''Third phase'''
:::The publication of final regulations in the form of drug monographs is the third and last phase of the review process. The monographs establish conditions under which certain OTC drug products are generally recognized as safe and effective.
===Clinical Trials : Rx-to-OTC===
Clinical trials are not a compulsory requirement for Rx-to-OTC switches, but most switch applications include new clinical trial data for the non-prescription indication and almost all the switch applications include label comprehension studies and/or actual use studies to demonstrate
that the medicine can be used safely and effectively in the consumer target population. Additional standard efficacy and safety clinical trials are to prove the drug can be used safely in an OTC setting.
FDA’s Center for Drug Evaluation and Research (CDER) defines OTC drug actual use study as “a controlled experiment in which a prescription drug or unapproved new drug is used by subjects under OTC-like conditions.” OTC studies are intended to support a significant change in labelling for the drug. These studies are considered the most important in assessing a drug’s appropriateness for a switch. The main Objectives of an Rx-to OTC study fall into four main categories:
# Safety (prescription safety demonstrated by previous trials)
# Comprehension (demonstrated by label comprehension studies)
# Self-selection and de-selection
# Compliance as the core issue
If the drug has a good safety profile, shown by the studies done to support its marketing as a prescription drug, and if the drug meets the specific criteria for switching which includes ability of selection or de-selection by consumer, there is relatively good chance that FDA will approve it for OTC use.
Source:[http://www.fda.gov/Drugs/DevelopmentApprovalProcess/SmallBusinessAssistance/ucm069917.htm FDA], [http://www.complianceonline.com/articlefiles/Regulatory_Requirements_Prescription_to_OTC_Switches_USA_India.pdf Compliance Online]
==Market Overview==